Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5 E, 00014 Helsinki, Finland; Orion Pharma R&D, Global Pharmaceutical Research, P.O. Box 65, 02101 Espoo, Finland.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, Viikinkaari 5 E, 00014 Helsinki, Finland.
Int J Pharm. 2020 Sep 25;587:119636. doi: 10.1016/j.ijpharm.2020.119636. Epub 2020 Jul 11.
Aqueous solubility of a drug substance is an important attribute affecting oral bioavailability. Nanonization, particle size reduction to submicron level, is an elegant approach to improve drug solubility and dissolution by increasing the surface energy, which in turn necessitates the use of stabilizers. The purpose of this study was to develop a nanosuspension of a practically water-insoluble investigational molecule by nanomilling approach using wet media milling. A variety of polymeric and surface active excipients were tested for their wettability. A combination of hydroxypropyl methylcellulose and sodium lauryl sulfate (SLS) were selected as stabilizers on the bases of compatibility studies and efficient wettability behaviour in contact angle measurements (≈80˚). A factorial design set-up was used to study the effect of milling bead diameter and stabilizer concentration on the efficiency of particle size reduction. Nanonization outcome was different when milling beads of 0.5 mm and 1 mm diameter were used at different concentrations of the stabilizers, which demonstrated the complex nature of the whole system. Storage of the nanosuspensions under different temperature conditions resulted only in minor changes of the particle size fractions.
药物的水溶解度是影响口服生物利用度的一个重要属性。纳米化，即将粒径减小到亚微米级，是一种通过增加表面能来提高药物溶解度和溶解速率的优雅方法，这反过来又需要使用稳定剂。本研究的目的是通过使用湿介质研磨的纳米研磨方法开发一种实用上不溶于水的研究分子的纳米悬浮液。对各种聚合物和表面活性剂辅料进行了润湿性测试。根据相容性研究和接触角测量（≈80˚）中有效润湿性行为，选择羟丙基甲基纤维素和十二烷基硫酸钠（SLS）的组合作为稳定剂。使用因子设计设置来研究研磨珠直径和稳定剂浓度对粒径减小效率的影响。当以不同浓度的稳定剂使用 0.5 和 1 毫米直径的研磨珠时，纳米化结果不同，这表明整个系统的复杂性。在不同温度条件下储存纳米悬浮液仅导致粒径分数的微小变化。
